2016
Gatlinburg Conference Symposium
SS‐15 Symposium Title: Executive Functions in Autism Spectrum Disorder, Down Syndrome, and Sex Chromosome Aneuploidy: An Examination of Age Effects and Relations with Comorbid Psychopathology Chair: Nancy R. Lee1 2, Gregory L. Wallace3 Discussant: Deborah Fidler4 Overview: Executive functions (EF) are important for the completion of everyday tasks that involve planning, self‐monitoring, organization, and the active maintenance of information in pursuit of a larger goal. Research suggests that virtually all developmental disabilities can be characterized by some degree of executive dysfunction, and it has been proposed that different developmental disorders can be characterized by different executive function profiles [1,2]. The proposed symposium seeks to integrate research on everyday executive functions, as measured by the Behavior Rating Inventory of Executive Function, in youth with autism spectrum disorder, Down syndrome, and sex chromosome aneuploidy paying particular attention to the following: (a) variation in EF skills as a function of age and (b) links with comorbid psychopathology. Paper 1 of 4 Paper Title: Age and Co‐Morbid Psychopathology are Associated with Everyday Executive Functioning among Children and Adolescents with Autism Spectrum Disorder Authors: Emily White2, Gregory L. Wallace3, Cara Pugliese5, Laura Anthony5, Alex Martin2, Lauren Kenworthy5 Introduction: It is now well established that executive functioning (EF) is developmentally dynamic during typical development, with variable trajectories depending upon the subcomponent EF process under investigation (e.g., working memory vs. inhibitory control vs. cognitive flexibility). EF difficulties are also associated with various forms of psychopathology, including anxiety, depression, and aggression. Among individuals with autism spectrum disorder (ASD) relatively little is known about how EF skills in everyday settings vary at different ages and relate to co‐morbid psychopathology. The first aim of the current study is to extend prior work by evaluating age‐related differences in parent‐reported EF problems during childhood and adolescence in a large cross‐sectional cohort of children with ASD. The second aim of the present investigation is to examine associations between these everyday EF problems and co‐morbid psychopathology. Methods: Children (n=210; 174 males) with an ASD without intellectual disability participated in the study and each had everyday EF and co‐morbid psychopathology rated by parents utilizing the Behavior Rating Inventory of Executive Function (BRIEF) and the Child Behavior CheckList (CBCL), respectively. Participants were divided into four groups based on age (5‐7, 8‐10, 11‐13, and 14‐18 year olds). Results: There were significant age effects (i.e., worsening scores with increasing age) on three BRIEF scales: Inhibit (p=.015), Initiate (p=.015), and Monitor (p=.019). In addition, when submitted to a regression accounting for age effects, both behavior regulation and metacognitive EF problems (from the BRIEF) predicted (p<.01) depression symptomatology. In contrast, age and behavior regulation problems predicted anxiety symptomatology, and behavior regulation problems alone predicted conduct problems (ps<.01). 1
Drexel University National Institute of Mental Health 3
George Washington University 4
Colorado State University 5
Center for Autism Spectrum Disorders, Children's National Health System 2
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SS‐15 Discussion: Older children with ASD show some evidence for greater EF problems compared with the normative sample than younger children with ASD. Specifically, there is a widening divergence from the normative sample in select EF subcomponents in children with ASD as they age. There were also strong associations between EF problems and co‐morbid psychopathology (i.e., anxiety symptoms, depression symptoms, and conduct problems). These findings have implications for the challenges faced by individuals with ASD without intellectual disability as they attempt to enter mainstream occupational and social environments. Much work is still needed. The gold standard approach for assessing age effects is the utility of a longitudinal design. We are currently in the final stages of collecting follow‐up BRIEF data in a relatively large proportion of these children and adolescents with ASD. Therefore, by the time of the conference, we also aim to profile for the first time longitudinal changes in everyday EF and their correlates in ASD. Paper 2 of 4 Paper Title: Real‐World Executive Functioning and its Clinical Correlates among Young Adults with Autism and Older Adults with the Broader Autism Phenotype Authors: Gregory L. Wallace3, Rebecca Charlton6, Haroon Popal2, Emily White2, Jessica Budgett6, Lauren Kenworthy5, Alex Martin2 Introduction: Although executive functioning (EF) difficulties are well documented among children and adolescents with autism spectrum disorder (ASD), little is known about real‐world measures of EF among adults with ASD. Therefore, we present two studies of real‐world EF and its associations with co‐morbid psychopathology in (1) young adults with ASD and (2) older adults with the Broad Autism Phenotype (BAP). Methods: Study 1 examined parent‐reported real‐world EF problems (from the Behavior Rating Inventory of Executive Function‐
Adult version) among 35 adults (ages 18‐40 years) with ASD without intellectual disability and how they correlated with co‐
morbid anxiety and depression symptomatology (using the Adult Behavior CheckList) and with adaptive functioning (using the Adaptive Behavior Assessment System‐Second Edition). Study 2 investigated for the first time the BAP (using the Broad Autism Phenotype Questionnaire) in the context of older adulthood and its associations with real‐world executive function (from the Behavior Rating Inventory of Executive Function‐Adult version), social support (Duke Social Support Index), and both depression (Geriatric Depression Scale) and anxiety (Beck Anxiety Inventory) symptomatology. Based on self‐ratings of autistic traits and the presence of family members with an autism spectrum disorder diagnosis, 66 older adults (60+ years old, range=61‐88) were split into BAP (n=24) and control (n=42) groups. Results: In study 1, a variable EF profile was found with the most prominent deficits occurring in flexibility and metacognition (ps<.001). Flexibility problems were associated with anxiety‐related symptoms (p<.01) while metacognition difficulties were associated with depression symptoms and impaired adaptive functioning (ps<.05). In study 2, individuals in the BAP group, even after controlling for age, education level, sex, and health problems (e.g., high blood pressure, diabetes) exhibited more real‐
world executive function problems in multiple domains (with a profile akin to prior studies of children [and to the study described above of adults] with ASD, including a peak deficit in flexibility), reported lower levels of social support, and self‐rated increased depression and anxiety symptomatology compared to the control group (ps<.001). Additionally, just as in study 1, flexibility problems were associated with anxiety‐related symptoms (p<.001) while metacognition difficulties (as well as flexibility problems in this case) were associated with depression symptoms (ps<.01). 6
Goldsmiths University of London Page 2 of 5 2016
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SS‐15 Discussion: Study 1 revealed that real‐world EF problems persist into adulthood in ASD and are strongly associated with both internalizing behaviors and adaptive functioning making EF an important treatment target among adults with ASD. Findings from study 2 suggest that the BAP in older adulthood could represent an additive risk factor in which normal age‐related declines are exacerbated by the presence of increased autistic traits. These results might in turn inform our understanding of aging in autism spectrum disorder, which has been largely unexplored to date. These two studies converge in demonstrating the continued importance of everyday EF throughout adulthood in ASD and the BAP. Just as studies of EF across childhood and adolescence in ASD suggest persistent flexibility difficulties, so too do these studies of young adults with ASD and older adults with the BAP. Moreover, both studies converge in demonstrating an emerging link between EF problems and psychopathology, specifically flexibility problems with anxiety symptoms and metacognition problems with depression symptoms. Given the relatively new EF‐based interventions for ASD in childhood, it is imperative to extend these upward developmentally as they may improve outcomes for adults with ASD. Paper 3 of 4 Paper Title: An Examination of The Relations Between Everyday Executive Functions, Age, and Psychopathology in Children and Young Adults with Down Syndrome Authors: Mary Godfrey1, Moshe Maiman1, Payal Anand7, Elizabeth Will4, Liv S. Clasen2, Lisa Daunhauer4, Deborah Fidler4, Jay Giedd2 8, Jamie Edgin7, Nancy R. Lee1 2 Introduction: Down syndrome (DS) is a developmental disorder characterized by a slowing of cognitive development from infancy to very early childhood [1,2], a precocious decline in executive function [EF] skills in later adulthood [3], and heightened rates of early onset Alzheimer's disease [4]. Less is known about the relationships between age and different cognitive abilities, such as EF skills, in childhood and young adulthood in this group. Thus, the current research sought to describe age‐EF relations in a sample of individuals with DS, ages 4‐24 years. In addition, it aimed to examine the behavioral correlates of parent‐reported EF skills by examining relations between scores on the Behavior Rating Inventory of Executive Function (BRIEF) and dimensions of psychopathology as measured by the Nisonger Child Behavior Rating Form (NCBRF). Methods: The sample included 85 youth with DS and 43 youth with typical development (TD), ages 4‐24 years. Parents completed either the preschool or school‐age version of the BRIEF and raw composite scores were calculated for five domains (Emotional Control, Inhibition, Shift, Working Memory, and Plan/Organize) by identifying identical or very similar items across the two forms of the BRIEF. In addition to completing the BRIEF, a subset of parents (n=22) also completed the NCBRF to measure different domains of psychopathology in youth with DS only. Results: To examine if age‐BRIEF relations varied as a function of group, hierarchical linear regression analyses were completed with the following steps: (1) age, (2) group, (3) age x group. Results revealed main effects of group across all composites (all ps < .01), main effects of age on the Inhibit composite (p<.05), but no group x age interactions (ps>.4). Rather, similar degrees of impairment were observed for youth with DS relative to the TD group over the age range studied for all five BRIEF domains. Relationships between BRIEF scores and dimensions of psychopathology/prosocial behavior were examined using stepwise linear regression (forward selection) to predict the following NCBRF scales: Conduct Problem, Insecure/Anxious, Self‐
Isolated/Ritualistic, Compliant/Calm, and Adaptive Social. (These scales were chosen in order to minimize item overlap between the BRIEF and NCBRF). For the Conduct Problem scale, the BRIEF Inhibit and Plan/Organize composites were significantly predictive of problem behaviors (all ps < .05). For the Insecure/Anxious and Self‐Isolated/Ritualistic scales, only the Emotional 7
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University of Arizona University of California, San Diego Page 3 of 5 2016
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SS‐15 Control composite of the BRIEF was significantly predictive (ps<.05). For both the Compliant/Calm and Adaptive Social scales, only the Inhibit composite was significantly predictive (p<.05). Discussion: These results suggest that difficulties on everyday EF tasks (as rated by parents) are similar in degree across middle childhood and young adulthood in DS. Moreover, a preliminary examination of EF‐psychopathology relations suggested that parent ratings of prosocial and problem behaviors in youth with DS were related to everyday EF skills falling into the Plan/Organize, Emotional Control, and Inhibit domains. These results will be discussed within the context of the larger DS cognitive‐behavioral phenotype and the possible importance of EF skills for adaptive behaviors and psychopathology. Lastly, limitations of this research, including the cross‐sectional sample and use of parent ratings of EF and psychopathology only, will be discussed with regard to the need for future research. References/Citations:  Carr J. (2005). J Intellect Disabil Res 49:915‐928.  Hodapp RM, Zigler E. (1990). Applying the developmental perspective to individuals with Down syndrome. In: Cicchetti DM, Beeghly, M, editors. Children with Down syndrome. New York: Cambridge University Press, p 1‐28.  Ball SL et al. (2008). Br J Clin Psychol 47:1‐29.  Lott IT. (1982). Ann N Y Acad Sci 396:15‐27. Paper 4 of 4 Paper Title: Variation in The Severity of Everyday Executive Function Skills in Relation to Age and Symptoms of Psychopathology in Youth With an Extra X Chromosome: A Comparison with Typical Youth and Youth with Down Syndrome Authors: Nancy R. Lee1 2, Elizabeth Will4, Elizabeth Adeyemi2, Liv S. Clasen2, Jonathan Blumenthal2, Lisa Daunhauer4, Deborah Fidler4, Jay Giedd2 8, Jamie Edgin7 Introduction: Executive functions (EF) are thought to be impaired in youth with sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X; [1]). However, little is known about developmental trajectories associated with EF difficulties in this group or the relations between everyday EF skills and psychopathology. Research studies using lab‐based measures of EF have suggested a relationship between these abilities and both attention‐deficit/hyperactivity disorder [2] and autism spectrum disorder symptomatology [3]. However, these relations have not been explored using a general measure of psychopathology that assesses emotional and behavioral difficulties across many domains. Thus, the current research examines this relationship as well as age‐EF relations in youth with +1X relative to youth with Down syndrome and those with typical development (TD). Methods: The sample included 30 youth with +1X, 30 youth with DS, and 30 youth with TD matched group‐wise on age, gender, and maternal education levels. Parents of all participants completed the school‐age Behavior Rating Inventory of Executive Function (BRIEF). In addition, a subset (n=24) of parents of youth with +1X also completed the Achenbach Child Behavior Checklist (CBCL) about their child. Results: To examine if age‐BRIEF relations varied as a function of group, hierarchical linear regression analyses were completed with the following steps: (1) age, (2) group, (3) age x group. Results revealed main effects of group across all scales (all ps < .01) and a main effect of age on the Inhibit scale, such that scores improved with age overall (p<.05). However, for the Initiate and Plan/Organize scales, the main effect of group was qualified by a group x age interaction (ps<.03), such that there was a trend in the data for higher scores on the BRIEF (denoting greater difficulties) with increasing age in youth with +1X only. Relationships between BRIEF scores and dimensions of psychopathology were examined using stepwise linear regression (forward selection) to predict scores on the different scales of the CBCL. Relationships between the BRIEF scales and three CBCL scales (of 8 scales Page 4 of 5 2016
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SS‐15 total) were noted. These were for Social (predicted by Monitor and Inhibit, ps<.05), Attention (predicted by Initiate only, p<.05), and Delinquent Behavior/Rule Breaking (predicted by Initiate only, p<.05). Discussion: Unlike youth with DS, there is a suggestion that certain everyday EF skills (initiation and planning/organization) are more deviant from peers at older ages for youth with +1X. Given the cross‐sectional nature of these data, these results must be interpreted with caution. However, from both a clinical and developmental perspective, it will be important to investigate these findings further, ideally using a longitudinal study design, in order to determine if greater attention should be paid to EF difficulties in adolescents with additional X chromosomes. Interestingly, relations between parent reports of EF difficulties and problem behaviors were very consistent with prior research utilizing laboratory EF measures in males with +1X. In particular, difficulties with monitoring and inhibition appeared to be related to social difficulties and difficulties with initiation appeared to be related to attentional difficulties and delinquent behavior. These results will be discussed in relation to the broader cognitive‐
behavioral and psychosocial phenotype for males and females with +1X, paying particular attention to disentangling executive dysfunction, externalizing behavior, and social impairments that are known to characterize males and females in this group. References/Citations:  Bender BG et al. (1993). Am J Med Genet 48:169‐173.  Lee, N.R. et al. (2011). J Int Neuropsychol Soc:1‐9.  Van Rijn, S. et al. (2012). J Psychiatric Research 46: 1300‐1306 Page 5 of 5